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. 2023 Dec;16(6):e004251.
doi: 10.1161/CIRCGEN.122.004251. Epub 2023 Oct 5.

Potential Diagnostic Role for a Combined Postmortem DNA and RNA Sequencing for Brugada Syndrome

Carlos Bueno-Beti #  1 , David C Johnson #  1 , Chris Miles  1 , Joseph Westaby  1 , Mary N Sheppard  1 , Elijah R Behr #  1 , Angeliki Asimaki #  1
Affiliations

Potential Diagnostic Role for a Combined Postmortem DNA and RNA Sequencing for Brugada Syndrome

Carlos Bueno-Beti et al. Circ Genom Precis Med. 2023 Dec.
No abstract available

Keywords: Brugada syndrome; autopsy; diagnosis; genetic testing; sodium.

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Conflict of interest statement

Disclosures Dr Behr has undertaken consulting for Boston Scientific in the last 3 years. The other authors report no conflicts.

Figures

Figure.
Figure.
Combined DNA-sequencing (DNAseq) and RNA-sequencing (RNAseq) analysis approach as a potential diagnostic tool in Brugada syndrome (BrS). Formalin-fixed paraffin-embedded (FFPE) heart tissue from the right ventricular outflow tract from 6 patients with BrS and 5 age- and sex-matched controls with a noncardiac death, were selected for this study. DNA and RNA from all samples were extracted and sequenced on an Illumina HiSeq instrument. Alignment was undertaken with STAR-2.7.3a on GRCh38. Quality control metrics were assessed by FastQC, QualiMap, RNASeqMetrics, and PICARD. FeatureCounts generated counts for each gene. To call variants, SplitNCigarReads, BaseRecalibrator, ApplyBQSR, and HaplotypeCaller were applied to aligned DNAseq and RNAseq in accordance with germline short variant discovery GATK (v4) guidance. A total of 198 genes were investigated. Differential expression between BrS cases and Control subjects was assessed using DeSeq2.27 (false discovery rate cutoff at 0.01). Gene set enrichment analysis was performed using all genes ranked by their differential mRNA expression. FH indicates family history; IRX3, Iroquois Homeobox 3; IRX5, Iroquois Homeobox 5; SCN5A, sodium voltage-gated channel alpha subunit 5; and VUS, variants of uncertain significance.
See this image and copyright information in PMC

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